The broad program described in this application represents a multi- faceted approach to the cell biology and metastasis. The studies will utilize syngeneic tumor lines which differ in their metastatic ability to determine the unique characteristics possessed by malignant cells which allow for their survival and growth in vivo. This is a new approach to the study of cell surface antigenicity as related to host defense mechanisms affecting tumor growth and spread. The ultimate objective of the experimental work is to determine the factors (tumor cells and/or host) which are responsible for the phenomenon of metastasis. Tumor cell characteristics such as rate of growth, cell surface charge, composition as related to their biological behavior will be studied. In addition host defense mechanisms (circulatory system, inflammation, immune stimulation, immune inhibition) and their relationship to tumor spread will be investigated. Also continuing studies will be conducted to determine the relationship between cellular mediated immunity and cancer spread (immune stimulation - inhibition) utilizing spontaneous canine tumors (primary and secondary) and studying these in vitro by a variety of techniques. Our studies will progress, correlate and incorporate findings from tissue culture, in vivo mouse systems, and spontaneous metastases in dogs.